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Interleukin‐22 (IL‐22) plays a key role in promoting antimicrobial immunity and tissue repair at barrier surfaces by binding to the receptors IL‐22R1, which is generally thought to be expressed exclusively in epithelial cells, and IL‐10R2. Our laboratory previously demonstrated that IL‐22 plays an important role in ameliorating liver injury in many rodent models by targeting hepatocytes that express high levels of IL‐22R1 and IL‐10R2. Recently, we have identified high expression levels of IL‐22R1 and IL‐10R2 in liver progenitor cells and hepatic stellate cells (HSCs). Overexpression of IL‐22 in vivo or treatment with IL‐22 in vitro promotes proliferation of liver progenitor cells via a signal transducer and activator of transcription 3 (STAT3)‐dependent mechanism. IL‐22 treatment also prevents HSC apoptosis in vitro and in vivo. Surprisingly, overexpression of IL‐22, via either gene targeting or exogenous …